pbs-5
C. elegans
Proteasome subunit pbs-5
What the model saw
Gene: pbs-5 Organism: Caenorhabditis elegans Known functions: Proteasome subunit pbs-5. endopeptidase activity. threonine-type endopeptidase activity.
View unredacted entry
Proteasome subunit pbs-5. endopeptidase activity. threonine-type endopeptidase activity.
Solver output
pbs-5 encodes a beta subunit of the 20S proteasome core particle in C. elegans, harboring the catalytic threonine-type endopeptidase activity responsible for cleaving ubiquitinated and damaged proteins. Robust proteasomal degradation is essential for proteostasis maintenance, clearing misfolded, oxidized, and aggregated proteins that accumulate with age. In C. elegans, enhanced proteasome activity (e.g., via rpn-6 overexpression or proteasome subunit upregulation) extends lifespan, while proteasome impairment accelerates aging and proteotoxic stress. The threonine-active-site mechanism of pbs-5 is the direct catalytic step that drives substrate degradation within the proteasome barrel, making its normal function central to proteostasis. Loss of pbs-5 function leads to accumulation of damaged proteins, a hallmark of aging, whereas its normal activity opposes this accumulation and supports longevity.
GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.
Advisor judgment
The model correctly predicted pro_longevity for pbs-5 with high confidence (0.82). The mechanistic reasoning is sound and well-detailed: pbs-5 encodes a catalytic beta subunit of the 20S proteasome with threonine-type endopeptidase activity, and proteasome function is well-established as pro-longevity in C. elegans. The model correctly identifies the ubiquitin-proteasome system and proteostasis network as key pathways, and appropriately references relevant literature context (rpn-6 overexpression studies). The reasoning logically connects proteasome activity to longevity through proteostasis maintenance and clearance of damaged proteins.
Raw API responses
solver
{
"reasoning": "pbs-5 encodes a beta subunit of the 20S proteasome core particle in C. elegans, harboring the catalytic threonine-type endopeptidase activity responsible for cleaving ubiquitinated and damaged proteins. Robust proteasomal degradation is essential for proteostasis maintenance, clearing misfolded, oxidized, and aggregated proteins that accumulate with age. In C. elegans, enhanced proteasome activity (e.g., via rpn-6 overexpression or proteasome subunit upregulation) extends lifespan, while proteasome impairment accelerates aging and proteotoxic stress. The threonine-active-site mechanism of pbs-5 is the direct catalytic step that drives substrate degradation within the proteasome barrel, making its normal function central to proteostasis. Loss of pbs-5 function leads to accumulation of damaged proteins, a hallmark of aging, whereas its normal activity opposes this accumulation and supports longevity.",
"confidence": 0.82,
"key_pathways": [
"ubiquitin-proteasome system (UPS)",
"proteostasis network",
"oxidative stress response / damaged protein clearance"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for pbs-5 with high confidence (0.82). The mechanistic reasoning is sound and well-detailed: pbs-5 encodes a catalytic beta subunit of the 20S proteasome with threonine-type endopeptidase activity, and proteasome function is well-established as pro-longevity in C. elegans. The model correctly identifies the ubiquitin-proteasome system and proteostasis network as key pathways, and appropriately references relevant literature context (rpn-6 overexpression studies). The reasoning logically connects proteasome activity to longevity through proteostasis maintenance and clearance of damaged proteins.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}